Disease-specific cost savings of treating nighttime versus daytime gastroesophageal reflux disease in an employed population

Summary

Objective: The extent to which proton pump inhibitors (PPIs) can offset direct medical costs by reducing symptoms related to gastroesophageal reflux disease (GERD) in order to improve work productivity is not well understood. This study aimed to evaluate the economic impact of treating GERD with PPIs versus no treatment, from an employer's perspective.

Study design: An economic model was developed to simulate symptom reduction and breakthrough symptoms as well as associated costs over 1 year among a population of 100,000 with a 20% GERD prevalence rate. Medical costs, including GERD-related office visits, hospitalisations and procedures, were delineated by symptom severity. Indirect costs represented the monetised work productivity loss. PPI treatment costs $2/day (standard dose).

Results: The GERD burden was substantial ($62,500,000). Treatment yielded $32,600,000 in savings ($1,630 saved/patient/year), mostly from reducing indirect costs. Treatment produced greater savings among nighttime GERD patients throughout the PPI cost range ($1–$5/day). Savings dropped if the price of standard doses of PPI exceeded $3.92/day for the treatment of daytime GERD patients.

Keywords::

• GERD
• nighttime GERD
• daytime GERD
• cost
• proton pump inhibitor
• productivity

Introduction

Gastroesophageal reflux disease (GERD) is a common digestive disorder characterised by frequent episodes of heartburn and acid regurgitation. These symptoms occur in approximately 7% of the adult population daily, 14–20% weekly and 36–44% monthly1. Approximately 19 million prevalent cases of GERD were reported in the US in 19982.

GERD is by far the most costly digestive disorder in the US, with an estimated $10 billion in direct and $15 billion in indirect costs per year in year 2000 dollars2. Indirect costs due to GERD-related work loss may exceed direct medical costs by a substantial margin2,3. These costs impose a significant financial burden on employers and health organisations that manage the care for this condition. Healthcare payers have focused on controlling the cost of care.

GERD patients who suffer from frequent nighttime symptoms may experience a greater degree of impairment compared with patients with symptoms confined to daytime. Approximately 80% of GERD patients experiencing daytime symptoms at least once per week reported nighttime heartburn, which can lead to sleep disturbance, limitations in next-day functioning, including work performance and absenteeism, and other decrements in quality of life4,5. A population-based survey documented that individuals with frequent nighttime symptoms of GERD experienced significantly greater work productivity loss compared with those with no or minimal nighttime symptoms6. A mean difference of 6.8% in total work productivity loss due to GERD-specific health problems was demonstrated for patients with frequent nighttime symptoms versus those with no or minimal symptoms (p<0.0001). This productivity difference represents nearly 2.72 hours per week of incremental work loss due to GERD among those with frequent nighttime symptoms compared with GERD patients without these symptoms.

Previous studies have evaluated the economic impact of treating GERD1,7–11. Several studies in the late 1990s focused only on the cost of healing erosive oesophagitis as opposed to symptomatic relief9,11. Compared with endoscopic endpoints, relief of symptoms is more applicable to standard clinical care because most patients with GERD are managed by symptom reduction in order to gauge treatment efficacy. Gerson et al reported that continuous proton pump inhibitor (PPI) therapy may yield greater clinical benefits compared with strategies using H₂ receptor antagonists (RA); however, the additional benefits from PPIs required additional costs7. They concluded that when assessing on-demand therapy alone, PPI therapy was the preferred strategy based on cost. However, a subsequent study by Goeree et al did not substantiate this conclusion; in this study, the preferred strategy involved PPI therapy followed by maintenance therapy with an H₂ RA to prevent symptomatic recurrence 8.

The prior economic studies had several limitations. First, the studies chose the perspective of a health services payer; consequently, they only included direct medical costs. Findings from these studies therefore underestimated the value of treating GERD, especially given recent evidence that this chronic condition can significantly impact work productivity, which is of importance to employers6. Therefore, it is conceivable that treating GERD with a PPI may lead to cost savings not through cost effectiveness but rather through cost offset (i.e. direct costs may be compensated by a reduction of indirect costs). Another limitation is that the studies did not differentiate between patients with frequent nighttime symptoms and GERD patients without these symptoms. Furthermore, previous studies did not explicitly model the reduction in costs as a function of reducing GERD-related symptom severity. A patient who only achieved a partial reduction in symptoms (e.g. from severe to moderate) should in theory achieve a partial benefit in terms of monetary value. There is evidence to support this assertion. One study reported that greater symptom severity is associated with more frequent GERD-related GP visits, GERD-related consultant visits and GERD-related hospitalisations even after controlling for patients’ age, gender and co-morbidity12. Louis et al reported that patients whose heartburn had slightly or severely affected their daily lives sought more physician visits and medical follow-up compared with those not affected by their heartburn13.

This model was undertaken to comprehensively evaluate the impact of treatment of GERD both on direct and indirect costs. In addition, the differential benefits with respect to treating patients with nighttime GERD (NG) versus daytime GERD (DG) were compared. PPIs were selected to represent the treatment comparator and untreated GERD was chosen as the reference group.

Patients and methods

A high-level, population-based model was constructed using Microsoft Excel (Microsoft Corp., Redmond, WA) to assess the direct and indirect costs of treating patients with GERD. A hypothetical cohort of patients treated continuously with PPI therapy was compared with a hypothetical cohort without any treatment over a 1-year period. These hypothetical patients were distributed across four GERD severity strata (i.e. mild, moderate, severe or no symptoms) at baseline. The model population experienced a shift in the distribution of symptom severity on treatment with a PPI or spontaneous symptom relief among those not on PPI therapies.

Figure 1 depicts the model scheme. In the hypothetical cohort receiving PPI therapy, patients received the standard daily dosage of PPI (i.e. the maintenance dose) for symptomatic relief of heartburn and acid regurgitation. After 4 weeks, a proportion of the cohort achieved complete relief and the remainder experienced either partial or no symptomatic relief. At the end of 6 months, a portion of those with complete relief experienced breakthrough symptoms that required a 1-month course of PPI at double the standard dose. Patients with either partial or no symptomatic relief at 4 weeks of treatment also received double the standard dose of PPI for 1 month. Thereafter, patients returned to a standard dose for the remainder of the year. Various patterns of PPI use exist in practice but only the pattern with daily PPI use was considered as this would be associated with the highest drug costs and bias against treatment, and thus yield more conservative results. In an alternative scenario, patients not taking PPI experienced complete spontaneous relief, partial relief or no relief of GERD-related symptoms during the first 6 months. Thereafter, symptoms could recur after 6 months among those who experienced spontaneous relief.

Figure 1.  Scheme for economic model comparing costs for PPI treatment versus no treatment.

Population

The model considered a hypothetical population of 100,000 with a 20% GERD prevalence rate14. In the comparison of DG versus NG, equal proportions of patients with DG and NG were assumed based on data collected from a published population-based survey15.

Model perspectives

The model was constructed from the perspective of employers.

Data on efficacy

Symptomatic response rates at 4 weeks on the standard dose of PPI, symptom breakthrough rates at 6 months and response rates after 4 weeks on a daily double dose of PPI were obtained from published literature. A search of PubMed was conducted to identify previously conducted systematic and comprehensive reviews of PPI efficacy studies. In addition, the Drug Class Review on PPIs conducted by the Oregon Evidence-Based Practice Center16 was included. From these sources, articles were selected that specifically focused on symptomatic outcomes as opposed to endoscopic outcomes for the specific time points of interest in this model (i.e. symptom relief after 4 weeks of treatment and breakthrough rates at 6 months). Studies of patients with erosive oesophagitis were separated from those with non-erosive oesophagitis. Most of these studies were conducted among patients with erosive oesophagitis (although a few included patients with non-erosive GERD). Three experts in gastroenterology reviewed the parameter estimates and provided a single estimate of each parameter, considering the distribution of erosive and non-erosive patients in the population. The base case value for each parameter was averaged from the responses of all experts. The range used in the sensitivity analysis was obtained from high and low estimates found in the literature or (when necessary) from the expert panel.

The symptomatic response rate after 4 weeks of PPI therapy at the standard dose was 56% (Table 1)18–28. The rate of breakthrough symptoms after 6 months of PPI therapy was 25% 29–31. The rate of symptomatic relief after 4 weeks of PPI double dosing was 77% 21, 22,24,25,27,32–45. Spontaneous relief without PPI treatment was assumed to be similar to the placebo response rate of 24% at 4 weeks observed in clinical trials (Table 1)18,19. The rate of breakthrough symptoms at the end of 6 months was 78%29,31.

Table 1.  Model parameters.

Parameter	Base value (%)	Range (%)	Reference
GERD prevalence	20	–	14
Proportion that are DG	50	–	Assumption based on 15
Proportion that are NG	50	–	Assumption based on 15
Baseline population distribution by GERD symptom severity
GERD
Mild	42.7	–	17
Moderate	45.4	–	17
Severe	11.9	–	17
DG
Mild	52.0	–	15
Moderate	42.5	–	15
Severe	5.5	–	15
NG
Mild	33.5	–	15
Moderate	48.4	–	15
Severe	18.1	–	15
% symptom relief at 4 weeks
PPI	56	26–84	18–28 and expert opinion
No treatment (placebo)	24	4–44*	18,19 and expert opinion
% breakthrough symptoms after 6 months
PPI	25	5–55^†	29–31 and expert opinion
No treatment (placebo)	78	62–90	29,31 and expert opinion
% symptomatic relief on double dose of PPI	77	35–92	21,22,24,25,27,32–45 and expert opinion
Distribution of symptom severity on treatment relapse
% mild	26	–	Expert opinion
% moderate	40	–	Expert opinion
% severe	34	–	Expert opinion
Cost parameters
Standard-dose PPI (daily)	$2	$1–$5	46
Hourly wage	$17.80‡	$8.91–$25.63^‡	48

GERD, gastroesophageal reflux disease; DG, daytime GERD; NG, nighttime GERD; PPI, proton pump inhibitor.

*The range chosen in the sensitivity analysis was ± 20% from the base case value because the two cited studies only included patients with NG.

^†The range chosen in the sensitivity analysis was ± 20% from the base case value because all cited studies only included patients with erosive oesophagitis.

^‡The base case value was based on the national average of all industry types. The low end of the sensitivity range was based on the ‘leisure & hospitality’ industry and the high end was based on the ‘utility’ industry.

Assumptions were necessary to determine the distribution of the population by severity strata for those patients who only experienced partial relief of symptoms. For patients with moderate or severe symptoms at baseline, 95% were predicted to achieve reduction to mild or no symptoms49. It was assumed that this 95% was equally distributed among the ‘mild’ and ‘no symptom’ categories. The remaining 5% who did not experience any relief remained at their baseline severity level. However, for the group with severe symptoms at baseline, the 5% were divided equally between the severe and moderate categories to allow for partial benefit.

Data on costs

An Internet-based survey of US adults aged ≥18 years was conducted to obtain self-reported GERD-related utilisation. The response rate from the survey was 15.4% (2,805 of 18,213). A total of 148 did not satisfy the survey entry criteria and 54 did not complete the survey. Among the 2,603 qualified respondents, the mean age was 45 years, 56% were women and 87% were White. Age and gender distributions of the respondents were comparable with the US population.

Direct medical costs

Dean et al reported that the overall average direct cost of GERD was $240 per patient per year, which included medical and procedure costs3. However, neither this study nor the general literature provided information to stratify costs by GERD symptom severity. Therefore, a series of steps were undertaken to estimate the relative utilisation weights that can be used to adjust the costs reported by Dean et al. First, each severity stratum was defined. The GERD Symptom & Medication Questionnaire (GERD-SMQ), a validated screening tool, was used to assess the presence of GERD during the previous 12 months50. GERD-SMQ scores range from 0 to 44, with scores greater than 9 indicating the presence of GERD. Next, severity of recent (from the past 3 months) symptoms of daytime and nighttime heartburn and acid regurgitation were assessed separately from the GERD-SMQ. Severity levels were assessed by four questions, each using a 10-point Likert scale ranging from ‘1 – very mild’ to ‘10 – very severe’. For the purposes of this study, severity was defined using the maximum value from the four measures. Respondents were then classified into the following severity groups: mild (1–4); moderate (5–7); and severe (8–10). Second, GERD-related utilisation was assessed by asking subjects to report their frequency of hospitalisation, emergency room visits, physician office visits, tests and procedures relating to GERD over the past 6 months51. This timeframe was chosen as a compromise between a shorter duration, which may result in infrequent or no GERD-related utilisation, and a longer duration, which may increase recall bias. To apply the 6-month utilisation data over the same 3-month period that GERD severity was assessed, it was assumed that the 3-month utilisation was one-half of the 6-month reported utilisation. Utilisation was stratified by GERD severity stratum and overall (Table 2). Third, utilisation of each component was converted into monetary value by applying publicly available fee schedules or payments (Table 3). Then, a utilisation weight was estimated for each severity stratum. Imputed costs for each severity stratum were summed and divided by the average total imputed cost among all cases to determine the utilisation weights relative to the ‘average’ GERD case (Table 4). Finally, the utilisation weights of 0.77, 0.84 and 1.52 were multiplied by $240, the published overall cost of GERD per year3, to derive the annual costs for patients with mild, moderate and severe symptoms (Table 4). All costs are reported in 2005 US dollars.

Table 2.  Self-reported utilisation per patient by GERD severity.

Self-reported utilisation per patient over the past 6 months	GERD severity			All*
	Mild	Moderate	Severe
Mean total hospitalisation days	0.019	0.021	0.030	0.023
Mean total times received ER care	0.026	0.038	0.173	0.066
Mean total no. of medical office visits	0.245	0.484	1.524	0.682
Mean no. of pH testing procedures	0.013	0.003	0.012	0.007
Mean no. of oesophageal testing procedures	0.006	0.003	0.012	0.006
Mean no. of oesophageal dilation procedures	0.013	0.006	0.030	0.013
Mean no. of gastric emptying study procedures	0.000	0.012	0.024	0.013
Mean no. of upper GI endoscopy procedures	0.058	0.047	0.113	0.067
Mean no. of endoscopy for anti-reflux procedures	0.013	0.018	0.042	0.026
Mean no. of upper GI radiography procedures	0.052	0.050	0.077	0.060

GERD, gastroesophageal reflux disease; ER, emergency room; GI, gastrointestinal. * This category represents all severity strata combined.

Table 3.  Unit costs for hospitalisation, medical visits and procedures.

Service	Code	Unit cost ($)*
GERD-related hospitalisation	DRG 155	5,788.4952
GERD-related ER visit	CPT 99285	161.2653
GERD-related office visit	CPT 99212	25.9353
Oesophageal acid testing (24-hour oesophageal pH test or capsule pH testing)	CPT 91034	270.6753
Oesophageal motility testing	CPT 91010	245.7353
Oesophageal dilation	CPT 4350, 4353, 4356, 4358	131.94^†53
Gastric emptying study	CPT 78264	230.8753
Upper GI endoscopy	CPT 43235	146.2253
Endoscopy to perform an anti-reflux procedure	CPT 43235	146.2253
Upper GI radiography that involves drinking barium	CPT 74246	113.4253

GERD, gastroesophageal reflux disease; DRG, diagnosis related group; ER, emergency room; CPT, common procedural terminology; GI, gastrointestinal.

* Costs are reported in 2005 US dollars.

^† The average among CPT codes 4350, 4353, 4356 and 4358.

Table 4.  Relative utilisation weights.

GERD severity stratum	Total costs of medical and procedure during the past 3 months ($)*	Relative utilisation weight	Estimated annual costs of GERD-related medical and procedure ($)
Mild	72.78 (A)	0.771^†	185
Moderate	78.80 (B)	0.835^‡	200
Severe	143.30 (C)	1.519^$	364
All	94.36 (D)	1.000 (reference)	240 (reference)^¶

GERD, gastroesophageal reflux disease.

* Costs were derived from utilisation data obtained from the Internet-based survey reported in Table 2 but were estimated for a 3-month time period by dividing by 2 then multiplying by the unit cost reported in Table 3.

^†Weight derived by dividing A by D.

^‡Weight derived by dividing B by D.

^$Weight derived by dividing C by D.

^¶The reference value of $240 was based on an analysis of claims data3.

Drug therapy-associated costs

The daily cost of standard dose PPI therapy was $2, based on the wholesale net price established in November 200546. The daily cost for a double dose of PPI was assumed to be $4. The cost of an office visit of $25.9353 was assigned to patients who initiated PPI therapy and who returned for follow-up visits due to symptom recurrence.

Indirect costs

Indirect costs were estimated from a published study that quantified the work productivity loss (absenteeism and presenteeism) by severity strata and by NG, DG and GERD (Table 5) expressed as the number of hours lost per 40-hour work week derived from the validated Work Productivity and Activity Impairment GERD-specific questionnaire^15,47,54,55. Absenteeism was defined as productivity loss while away from work and presenteeism was defined as productivity loss experienced during work56. The national average hourly earning of $17.80 in 200548 was applied to those hours lost to calculate productivity loss for each severity stratum.

Table 5.  Work productivity impairment by severity and GERD type54.

GERD severity	GERD (n=1,002)		DG (n=469)*		NG (n=475)*
	GERD WPAI (%)	Hours lost^†	GERD WPAI (%)	Hours lost^†	GERD WPAI (%)	Hours lost^†
Mild	4.6	1.8	3.3	1.3	6.6	2.6
Moderate	11.4	4.6	7.7	3.1	14.5	5.8
Severe	15.3	6.1	11.5	4.6	16.4	6.6

GERD, gastroesophageal reflux disease; DG, daytime GERD; NG, nighttime GERD; WPAI, Work Productivity and Activity Impairment.

*Fifty-eight cases were excluded because missing data did not permit assignment of DG and NG. Therefore, the results reported for GERD are not the arithmetic means of the DG and NG results.

^† The number of hours lost was calculated by multiplying the GERD WPAI percentage by a 40-hour work week (assumed).

Other assumptions

Other assumptions were necessary to simplify the model. It was assumed that the benefit of PPI therapy was the same for patients with DG and NG, and data on efficacy were obtained from studies of general GERD patients. The true total direct costs of not treating GERD are unknown. Therefore, the model used direct cost data from a group of patients already receiving PPI treatment and assumed that these costs were also relevant among the untreated GERD patients. The model assumed that breakthrough GERD symptoms occurred at 6 months and that patients sought care for breakthrough symptoms at that time. In reality, symptoms can occur at any time. It was also assumed that PPI therapy became efficacious immediately after initiation. The model did not account for patients who were lost to follow-up over the 1-year period because of mortality or attrition.

Sensitivity analyses

One-way sensitivity analyses were conducted on key clinical parameters and reported using a Tornado diagram. The cost of daily PPI was varied from $1 to $5.

Results

PPI treatment versus no treatment of GERD

The model estimated an overall cost of $62.5 million if GERD remained untreated in a hypothetical population of 100,000 with 20,000 cases of GERD (Table 6). Nearly all (93%) of this cost came from work productivity loss. PPI treatment increased the overall direct costs (from $4.5 million to $21.1 million) but decreased indirect costs (from $58.0 million to $8.8 million). When all costs were considered, treatment resulted in overall savings of $32.6 million ($1,630 in savings per treated patient per year) driven mostly by lower ‘indirect’ costs compared with no treatment.

Table 6.  Annual economic impact of treating GERD with proton pump inhibitors*.

Costs ($)^†	GERD (n=20,000)^‡
	Treatment	No treatment
Direct costs	21,073,248	4,505,187
Indirect costs	8,849,039	58,021,412
Total	29,922,287	62,526,599
Net savings	32,604,312
Savings per treated patient per year	1,630

GERD, gastroesophageal reflux disease.

*Based on a population of 100,000.

^†Costs reported in 2005 US dollars.

^‡The economic impact of treatment for GERD was derived from inputs specific for the GERD group rather than based on inputs from daytime GERD and nighttime GERD.

Treatment of patients with daytime GERD versus nighttime GERD

Similar trends were observed in the treatment of patients with DG and NG (Table 7), but treatment was associated with greater savings among NG patients ($2,387 vs. $733 per patient per year; $23.9 million vs. $7.3 million overall). Work productivity loss accounted for most of the economic impact, and patients with NG experienced greater impairment of productivity ($38.9 million vs. $18.5 million annually per 10,000 patients).

Table 7.  Comparison of the economic impact of treatment with proton pump inhibitors* among DG versus NG.

Costs ($)^†	DG (n=10,000)		NG (n=10,000)
	Treatment	No treatment	Treatment	No treatment
Direct costs	10,525,939	2,161,981	10,547,164	2,340,596
Indirect costs	2,840,527	18,536,187	6,780,510	38,858,299
Total	13,366,465	20,698,168	17,327,674	41,198,895
Net savings	7,331,703		23,871,221
Savings per treated patient per year	733		2,387

DG, daytime gastroesophageal reflux disease; NG, nighttime gastroesophageal reflux disease.

*Based on a population of 100,000.

^† Costs were reported in 2005 US dollars.

Sensitivity analyses

The savings associated with treating DG disappeared if the price of daily regular doses of PPI exceeded $3.92. In contrast, results supporting treating NG were robust when varied from $1 to $5 per day for standard dosing of PPI. Per-patient savings ranged from $2,770 when PPI was priced at $1 per day to $1,240 when priced at $5 per day.

Figure 2 represents a Tornado diagram showing the key parameters tested in one-way sensitivity analyses. Savings existed for treatment of GERD with PPI therapy over all plausible ranges of inputs examined.

Figure 2.  Tornado diagram of key parameters showing per patient savings from treatment of gastroesophageal reflux disease with PPIs.

Discussion

For most employers, assessing worker productivity is a challenge, let alone assessing the impact of a chronic medical condition on productivity. As this is the case, this cost has been unknown to many employers. This study showed that the economic burden of GERD is substantial if left inadequately treated. The model estimated the cost impact to be approximately $62.5 million per year for 20,000 cases of GERD. The majority of this financial burden came from loss of work productivity. Furthermore, the productivity loss did not come primarily from absenteeism but mostly from reduced productivity while at work (i.e. presenteeism)3. This fact should be of concern to employers, who traditionally may evaluate the value of their dollars spent on healthcare by assessing their healthcare budget silo or days absent from work.

This model has shown a net saving from treatment with PPIs from the perspective of employers. Approximately 75% of the nearly 19 million suspected GERD cases are working-age individuals2. Adopting a health services payer perspective (i.e. ignoring the indirect costs), this model would conclude that treatment results in better clinical benefits but at a substantial cost. The model demonstrated increases in costs from associated office visits, procedures and PPI drug therapies. Therefore, if only direct costs are considered, there are no net savings for health plans. From a health plan's perspective, promotion of GERD treatment will depend on whether the additional clinical benefits justify the additional costs. In contrast, when the employer's perspective is taken, the impact of treatment versus no treatment on work productivity becomes extremely relevant. Treatment of GERD was shown to be associated with a substantial reduction in indirect costs. With PPI treatment, the increase of $16.6 million in total direct costs was offset by $49.2 million in savings from improved productivity (indirect costs), resulting in net annual savings of $32.6 million (Table 6). This translated to $1,630 savings per GERD patient treated per year. For employers, these savings come from maintaining work productivity.

Treating patients with NG could result in greater economic savings compared with treating patients with DG. The net savings among 10,000 NG patients and 10,000 DG patients were $23.9 million vs. $7.3 million, respectively. These results were influenced by several factors. First, NG patients had more severe symptoms compared with DG patients. At baseline, approximately three-fold more NG patients than DG patients experienced severe GERD symptoms (Table 1)15. Second, patients with NG, on average, experienced greater productivity loss compared with patients with DG in every GERD severity stratum as reported by Dubois et al15. These factors combined resulted in untreated patients with NG having higher overall costs compared with untreated patients with DG. Patients with NG had greater indirect costs owing to a greater loss of productivity compared with DG patients.

The reported savings from PPI therapy were observed over a wide range of PPI costs tested in the sensitivity analysis. This suggests that the results from the model are robust over the range of plausible costs of PPIs. With the emergence of lower-cost PPI generic equivalents on the market, these estimated savings will likely increase.

The economic impact of GERD in this model may have been underestimated. The risk of developing complications from untreated GERD was not considered in this analysis (e.g. oesophageal strictures, Barrett's oesophagus or even oesophageal adenocarcinoma), nor was the human toll of patients suffering from the symptoms of GERD and their complications, unrelated to productivity impairment.

The model estimated the direct costs of treatment with PPI therapy to be approximately $21.1 million among 20,000 patients with GERD, which translates to approximately $1,055 per patient. By comparison, data from the American Gastroenterological Association were used to derive a cost of approximately $700 per patient adjusted for inflation ($9.325 billion among 18.6 million patients in 1998)2. It is plausible that the cost per patient is higher in this case due to the fact that this study modelled daily use of PPI instead of intermittent use of less expensive therapies (e.g. antacids, H₂ RA). The medical portion of the direct costs in the model was based on the estimate by Dean et al of an annual GERD-related cost per patient of $2403. This was lower than that from a more recent study by Brook et al, who reported that the annual GERD-related cost was $2,725 per patient57. Using this estimate in the model could increase direct medical cost by 10-fold.

This study has made several important contributions to the literature. First, this model included both direct and indirect costs. To date, most economic models conducted to evaluate the value of PPI therapy have not included the impact of treatment on indirect costs; consequently, they have underestimated the complete value of PPI therapy from a broader perspective1,7–11. This could have important implications in clinical care because decisions regarding access to PPI therapy have traditionally been based on studies that only included impact on direct costs. An appraisal of return on investment in medical benefits (particularly in settings where employers and/or the government are the ultimate payers) should theoretically consider how improved health states can lead to greater work productivity. This study has demonstrated that work productivity loss can successfully be accounted for in a modelling study of GERD. This approach could apply to evaluating therapies in other medical conditions.

Second, using an Internet-based survey, it was reported that patients having more severe GERD-related symptoms have greater self-reported utilisation for the condition. Although these findings validate a logical relationship, to the author's knowledge they are the first to report costs stratified by severity of GERD symptoms.

As with most economic models, assumptions were necessary when data for inputs were unavailable, and simplification was necessary to be pragmatic. Consequently, the results should be appraised in light of these limitations. First, the true direct costs among an untreated GERD population are unknown; therefore, the model used information on direct cost from a group of patients already receiving treatment and assumed that these costs were also relevant among the untreated GERD patients. This may have led to a lower net difference between comparators and thus may have underestimated the impact of treatment. Second, this model did not consider other treatment strategies for GERD such as intermittent or on-demand PPI therapy. Studies have suggested that patients who initially responded to therapy do not require continuous treatment until symptom relapse occurs. These strategies would result in a lower cost of PPI therapy compared with daily use of PPIs; therefore, greater savings from treatment may be expected. In this regard, the savings from comparing daily treatment using PPIs with no treatment was conservative. Third, other treatment options such as H₂ RA were not evaluated; future enhancements to the model should address these comparators. Fourth, this model allowed for only one chance of symptom recurrence within 1 year. If bothersome symptoms persist, repeat visits to the physician office are likely to occur and contribute to direct costs. Fifth, this model applied symptom relief rates from randomised controlled trials (RCTs). Taking into account the possibility of real-world lower adherence to PPI therapy, it is conceivable that response rates could be lower than those observed in RCTs. However, savings were predicted even after the symptom relief rate was decreased by approximately one-half (from 56 to 26%) in the sensitivity analysis. Lastly, this model relied on utilisation weights estimated from a survey of self-reported utilisation to determine cost in each severity stratum. Patients with mild symptoms may have less utilisation compared with patients with moderate or severe symptoms. However, it is possible that the true utilisation is greater among patients who suffer from mild symptoms owing to recall bias and consequently this could affect the estimation of utilisation weights. The likelihood of this phenomenon is low given that the utilisation weights of patients classified with mild and moderate symptoms were similar.

Conclusions

In summary, this model demonstrated the value of treating patients with GERD using PPI therapy. If left untreated, GERD can have a substantial economic impact, mostly in the form of work productivity loss. The value to employers whose employees are suffering from NG is particularly noteworthy because this subgroup is more likely to have more severe symptoms and they tend to experience greater work productivity impairment while at work. These savings appear to justify the use of PPI therapy for treatment of patients with moderate to severe GERD.

Acknowledgements

Declaration of interest: This study was supported by Wyeth Pharmaceuticals.

QV Doan, D Aguilar, E Reyes and RW Dubois work for an organisation that provides consultancy services to Wyeth. SM Lange and A Elfant are independent consultants to Wyeth and RB Lynn is an employee of Wyeth and owns shares in the company.

The authors wish to thank Lisa Kaspin for her editorial review of the manuscript.

Notes